Loss of Y chromosome in the malignant peripheral nerve sheet tumor of a patient with Neurofibromatosis type 1

Abstract

Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal dominant disorders. In order to determine whether genomic alterations and/or chromosomal aberrations involved in the malignant progression of NF1 were present in a Korean patient with NF1, molecular and cytogenetic analyses were performed on the pathologically normal, benign, and malignant tissues and primary cells cultured from those tissues of the patient. The comparative genomic hybridization (CGH) array revealed a Y chromosome loss in the malignant peripheral nerve sheet tumor (MPNST) tissue. G-banding analysis of 50 metaphase cells showed normal chromosomal patterns in the histopathologically normal and benign cultured cells, but a mosaic Y chromosome loss in the malignant cells. The final karyotype for the malignant cells from MPNST tissue was 45,X,-Y[28]/46,XY[22]. The data suggest that the somatic Y chromosome loss may be involved in the transformation of benign tumors to MPNSTs.

Keywords: CGH Array; Chromosome Loss; G-banding; Nerve Sheath Neoplasms; Neurofibromatosis 1, Y chromosome.

Fig. 1

CGH array profiles of the normal, benign and malignant tissues of a patient with NF1. Graphics from the Macrogen's Mac-Viewer array CGH software show that CGH array profiles for whole chromosomes by (A) hybridization of non-NF1 male DNA (reference) versus test DNA from normal tissue of the NF1 patient, (B) hybridization of DNA from normal tissue versus DNA from benign tissue of the NF1 patient, and (C) hybridization of DNA from normal tissue vs. DNA from MPNST tissue of the NF1 patient. Arrow indicates where loss occurred in the Y chromosome. (D) Graphic shows detailed CGH array profile for the whole region of Y chromosome in the hybridization of DNAs from normal tissues vs. MPNST tissues of the NF1 patient. Two markers with a letter 'C' indicate the position of centromere.

Fig. 2

GTG-banded karyotypes of the benign and malignant fibroblast cells from a NF1 patient. (A) Normal karyotype, 46,XY, was detected in metaphases of the benign cells. (B) Abnormal karyotype of loss of Y chromosome, 45,X,-Y, was detected in metaphases of the malignant cells. Arrow indicates where loss occurred in the Y chromosome.